Hot Line - Does assessment of coronary plaque activity predict recurrent CV events?

Reliable methods for predicting myocardial infarction (MI) in patients with obstructive coronary artery disease (CAD) are lacking. A previous retrospective post-hoc analysis suggested that non-invasive assessment of coronary plaque activity may be an effective way to determine the risk of MI in patients with CAD.¹

In a Hot Line session yesterday, Professor David Newby (University of Edinburgh - Edinburgh, UK) presented results from the PRE¹⁸FFIR trial, the first multicentre international study to prospectively investigate whether non-invasive assessment of coronary atherosclerotic activity predicts recurrent cardiac events following MI.

In this longitudinal observational cohort trial, patients aged over 50 years with recent MI (within 21 days) and multivessel CAD on invasive coronary angiography or previous coronary vascularisation were recruited. All participants underwent ¹⁸F-sodium fluoride (¹⁸F-NaF) positron emission tomography (PET) and computed tomography coronary angiography. Total coronary atherosclerotic plaque activity (coronary microcalcification activity [CMA]) was assessed using coronary ¹⁸F-NaF uptake, by an independent, blinded, core laboratory. Low activity was defined as CMA=0 and high activity as CMA>0. The originally designated primary endpoint of cardiac death or non-fatal MI was expanded during the study to include unscheduled coronary revascularisation when the primary event rates were lower than anticipated.

Of the 704 enrolled patients, 89% had multivessel CAD, 7% had left main stem disease and 4% had one-vessel disease. Plaque activity was designated as CMA=0 in 283 patients and CMA>0 in 421 patients, with similar mean Global Registry of Acute Coronary Events (GRACE) scores and CAD severity between the groups.

At a median follow up of 4 years, the primary endpoint occurred in 18% of patients with CMA=0 and 21% with CMA>0. Increased coronary atherosclerotic plaque activity was not found to be significantly associated with the primary endpoint (hazard ratio [HR] 1.25; 95% CI 0.89 to 1.76; p=0.20).

This was principally due to the lack of an association with unscheduled coronary revascularisation (HR 0.98; 95% CI 0.64 to 1.49; p=0.91). Secondary analyses showed increased coronary atherosclerotic plaque activity was linked with both all-cause mortality (HR 2.43; 95% CI 1.15 to 5.12; p=0.020) and the original primary endpoint of cardiac death or non-fatal MI (HR 1.82; 95% CI 1.07 to 3.10; p=0.028).

Prof. Newby comments: “Increased coronary atherosclerotic plaque activity is not associated with all coronary events but predicts cardiac death or non-fatal MI and all-cause mortality. The association remained after adjusting for the severity of obstructive CAD or GRACE score.” These findings support the hypothesis that coronary atherosclerotic plaque activity might predict spontaneous recurrent atherothrombotic events. CMA assessment could potentially be used to guide the application of more intensive lipid-lowering, anti-inflammatory or other advanced therapies to prevent recurrent spontaneous atherothrombotic events.